Antiinflammatory properties of tiotropium bromide: Reduction of macrophage induced chemotaxis in vitro

Introduction: Muscarinic receptor antagonists such as ipratropium bromide and tiotropium bromide are regularly used for the treatment of COPD. They may have anti-inflammatory properties due to inhibition of inflammatory effects related to prolonged stimulation of muscarinic receptors on airway smooth muscle cells and inflammatory cells. The purpose of this study was to evaluate tiotropium to reduce chemotaxis in vitro.

Methods/Results: Chemotaxis of neutrophils (PMN) was measured using LPS (1µg/ml, 20h) activated alveolar macrophages (AM) derived from smokers with COPD (n=14). The amount of migrated PMN with or without preincubation of AM with tiotropium bromide was quantified using a fluorescence detection assay. Tiotropium related reduction of PMN chemotaxis increased gradually from 3.0±1% (at 0,1 nM) to 24.1±15.0% (at 30 nM; p<0,01). Interestingly, cell survival rate increased in LPS exposed AM under tiotropium co-culture by 5.9% (3 nM), 14.7% (30 nM) and 24.5% (300 nM) (p<0.01).

Conclusion: Tiotropium reduces dose dependent AM mediated PMN chemotaxis. Further, tiotropium was shown to protect AM from LPS mediated toxicity. This in vitro study emphasize additional anti-inflammatory effects from tiotropium, which may be from relevance in in vivo use.

Supported by: Unrestricted grant from Boehringer Ingelheim, Germany